Claustrum Involvement in New Onset Refractory Status Epilepticus: A Systematic Review

Area of Science:

• Neurology
• Neuroimaging
• Epilepsy Research

Background:

• The claustrum sign, bilateral T2/FLAIR hyperintensity in the claustrum, is associated with new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES).
• Understanding the clinical significance of the claustrum sign is crucial for managing these severe epilepsy syndromes.

Purpose of the Study:

• To systematically review and compare clinical characteristics, treatments, and outcomes of NORSE/FIRES patients with and without the claustrum sign.
• To evaluate the diagnostic and prognostic implications of the claustrum sign in NORSE/FIRES.

Main Methods:

• A systematic literature search was performed adhering to PRISMA guidelines (2018-2026).
• Included peer-reviewed studies reporting MRI findings and patient-level data for NORSE/FIRES.
• Compared clinical data between patients with and without the claustrum sign.

Main Results:

• Of 206 NORSE cases, 72 exhibited the claustrum sign, predominantly in cryptogenic NORSE with febrile onset (93%).
• Patients with the claustrum sign had higher rates of convulsive status epilepticus (SE) but lower rates of super-refractory SE (SRSE) and ICU admission compared to those without.
• Claustrum sign was detected in 68/71 patients during the acute phase, typically 7 days post-SE onset; immunotherapy was common (92%).

Conclusions:

• The claustrum sign is a significant neuroimaging marker in NORSE/FIRES, often associated with febrile onset and convulsive SE.
• Recognition of the claustrum sign may facilitate earlier diagnosis and guide targeted therapeutic strategies.
• Further research is warranted to elucidate the pathophysiological role of the claustrum in these epilepsy syndromes.